Acute cytomegalovirus infection modulates the intestinal microbiota and targets intestinal epithelial cells

Le‐Trilling, Vu Thuy Khanh; Ebel, Jana‐Fabienne; Baier, Franziska; Wohlgemuth, Kerstin; Pfeifer, Kai Robin; Mookhoek, Aart; Krebs, Philippe; Determann, Madita; Katschinski, Benjamin; Adamczyk, Alexandra; Lange, Erik; Klopfleisch, Robert; Lange, Christian M.; Sokolova, Viktoriya; Trilling, Mirko; Westendorf, Astrid M. (2023). Acute cytomegalovirus infection modulates the intestinal microbiota and targets intestinal epithelial cells. European journal of immunology, 53(2), e2249940. Wiley 10.1002/eji.202249940

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Primary and recurrent cytomegalovirus (CMV) infections frequently cause CMV colitis in immunocompromised as well as inflammatory bowel disease (IBD) patients. Additionally, colitis occasionally occurs upon primary CMV infection in patients who are apparently immunocompetent. In both cases, the underlying pathophysiologic mechanisms are largely elusive - in part due to the lack of adequate access to specimens. We employed the mouse cytomegalovirus (MCMV) model to assess the association between CMV and colitis. During acute primary MCMV infection of immunocompetent mice, the gut microbial composition was affected as manifested by an altered ratio of the Firmicutes to Bacteroidetes phyla. Interestingly, these microbial changes coincited with high-titer MCMV replication in the colon, crypt hyperplasia, increased colonic pro-inflammatory cytokine levels, and a transient increase in the expression of the antimicrobial protein Regenerating islet-derived protein 3 gamma (Reg3γ). Further analyses revealed that murine and human intestinal epithelial cell lines, as well as primary intestinal crypt cells and organoids represent direct targets of CMV infection causing increased cell death. Accordingly, in vivo MCMV infection disrupted the intestinal epithelial barrier and increased apoptosis of intestinal epithelial cells. In summary, our data show that CMV transiently induces colitis in immunocompetent hosts by altering the intestinal homeostasis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Tissue Bank Bern
04 Faculty of Medicine > Service Sector > Institute of Pathology > Inflammatory Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Translational Research Unit

UniBE Contributor:

Mookhoek, Aart, Krebs, Philippe

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0014-2980

Publisher:

Wiley

Language:

English

Submitter:

Philippe Krebs

Date Deposited:

18 Oct 2022 10:04

Last Modified:

03 Feb 2023 00:13

Publisher DOI:

10.1002/eji.202249940

PubMed ID:

36250419

BORIS DOI:

10.48350/173832

URI:

https://boris.unibe.ch/id/eprint/173832

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